The water level change in the Great Lake region can modulate stresses in the nearby fault system and potentially induce earthquakes. We perform a systematic analysis of local seismicity around southern Lake Erie during 2013–2020 to investigate the relation between seismicity and lake water level change. We obtain a newly detected catalog of tectonic earthquakes, which reveals 20–40 M > 0 earthquakes/yr before 2019. The peak seismicity rate in 2019 is dominated by active aftershocks following the 2019 ML 4.0 Ohio earthquake. The clustering analysis reveals both clusters with multiple events and stand‐alone events that might represent isolated zones of crustal weakness in this region. The absolute location analysis identifies a group of earthquakes around the epicenter of the 1986 M 5 earthquake, which might be linked to the nearby injection activities. To evaluate the potential interaction with changing water loading of Lake Erie, we then model the coulomb stress change (ΔCSC) caused by elastic lake‐water loading and find that ΔCSC strongly depends on effective friction coefficient (μ). Considering the geometry of the receiver fault, higher lake water level results in positive ΔCSC and would promote failure when μ0.3, and leads to negative ΔCSC and would discourage rupture when μ>0.3. Further analysis indicates a lack of temporal correlation between long‐term seismicity and water level variations before the 2019 Ohio sequence, suggesting that water level fluctuations do not modulate long‐term seismicity. However, we cannot fully rule out the impact of increasing water level on reactivating the fault that hosted the 2019 Ohio earthquake sequence because of the uncertainty of μ. Our results highlight the necessity of denser and closer monitoring of lake seismicity to further investigate the impact of changing water loading on reactivating shallow faults in this region.

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